Recent outbreak of zika virus in India amid ongoing COVID-19 and monkeypox outbreak: A call for action
Authors: Ranjit Sah, Aroop Mohanty, Diptanu Paul, Bijay Kumar Padhi
Journal: International Journal of Surgery (2023)

Dear Editor,Highlights Zika virus (ZKV) is an arbovirus transmitted mainly by mosquitos belonging to the genus Aedes which is also known to transmit dengue and chikungunya. Congenital zika syndrome (CZS) developed in neonates if the mother gets infected during pregnancy. CZS with neonatal complications like congenital microcephaly, congenital glaucoma, optic neuropathy, ventriculomegaly, and lissencephaly are the most severe complications. Just when we are busy tackling some of the significant mosquito-transmitted viral infections like dengue, chikungunya, another re-emerging but old nemesis, ZKV, has marked its presence with fresh new cases. A fresh new victim of ZKV infection has been reported from India in a 5-year-old girl involving a new state Karnataka (Raichur district), with its first-ever case for the same1. Since 2016, it has been reported from India's 16 different states/union territories, Karnataka being the latest one; affirms the possibility of the virus getting endemic in this part of the world too2,3. ZKV was first discovered from the rhesus monkey (1947) and isolated from the Aedes mosquito (1948) in the Zika Forest, Uganda4. Later, the first human cases were detected in Nigeria, Tanzania, and Uganda in 1952. The first significant outbreak of ZKV infection occurred in the Yap islands of Micronesia, with 49 confirmed cases5. Following which two significant epidemics during 2013–14 in French Polynesia (∼30 000 cases) and 2015–16 in South American countries (~1.3 million cases) compelled the WHO to declare the situation a Public Health Emergency of International Concern (PHEIC) on 1 February 20166. Currently, ZKV cases are reported from 89 countries; the highest is from the South American region. From India, the first cluster of ZKV cases was reported from Gujarat (three cases) and Tamil Nadu (one case) in 2016–177. During 2018, as many as 159 cases, including 64 pregnant females, were reported from the state of Rajasthan, and 130 cases were reported from Madhya Pradesh, marking the biggest outbreak of ZKV in Southeast Asia8. Recently, ∼70 cases were detected in Kerala from July to August 20219. ZKV belongs to the family Flaviviridae and genus Flavivirus, a positive sense, single-stranded, enveloped RNA virus. Along with ZKV, other menacing family members, like the Japanese encephalitis virus, dengue virus, West Nile virus, and yellow fever viruses, are also transmitted by the vector mosquito. ZKV has a genome of 10 794 kbp with two noncoding regions and a long open reading frame coding for four structural (two envelope proteins, one capsid, and one membrane protein precursor) and seven nonstructural proteins. The major surface protein is the envelope protein responsible for binding and fusion. ZKV is an arbovirus transmitted mainly by mosquitos belonging to the genus Aedes which is also known to transmit dengue and chikungunya. The major Aedes species found to be responsible are A. aegypti, A. albopictus, A. hensilli, A. polynesiensis, and A. africanus. The presence of A. aegypti has been recorded in 61 countries, increasing the risk of ZKV transmission and its related dangers9. Moreover, the abundance of A. aegypti in tropical regions and A. albopictus in temperate regions makes these areas vulnerable to potential ZKV transmission. The ZKV also maintains two transmission cycles: the enzootic transmission cycle between Aedes mosquitoes and nonhuman primates and the urban transmission cycle carried between Aedes mosquitoes and humans. There are possible ways of nonvector-borne virus transmission also, like from mother to child, via blood transfusion, organ/bone marrow transplantation, sexual route, nosocomial, or accidental laboratory transmission. The clinical features of the ZKV infection create confusion with other mosquito-borne flaviviral infections. The usual incubation period is 3–12 days; however, 80% of the infections are asymptomatic. Acute infections are usually mild, with a self-limiting course of fever, joint pain, headache, rash, and gastrointestinal symptoms. However, CZS with neonatal complications like congenital microcephaly, congenital glaucoma, optic neuropathy, ventriculomegaly, and lissencephaly are the most severe complications feared in neonates if the mother gets infected during pregnancy. Such severe complications came into the picture during the Brazil outbreak in 2016, but inconsistencies were reported in 20% of patients10. In adults, an association between ZKV infection and a consequential autoimmune disorder causing progressive muscular illness – Guillain Barre syndrome, has been strongly suspected when cases of Guillain Barre syndrome spiked during ZKV outbreaks in French Polynesia (2013–14) and the Americas (2015–16)11. Other severe complications like arthralgia and cardiovascular complications are of uncertain significance. Rare complications like thrombocytopenia and testicular damage are also reported in some studies. Various studies have tried to identify the pathogenesis of the ZKV, concluding the involvement of different cellular receptors responsible for viral attachment like – DC-SIGN, heat shock proteins, and phosphatidylserine receptor proteins (TIM, AXL, TYRO). The AXL receptors are found abundantly in developing fetal brain cells, which makes them vulnerable to ZKV attachment. Moreover, several studies have found the ability of ZKV to infect human neural progenitor cells efficiently, leading to cause microcephaly and other brain abnormalities. These studies also reported reduced numbers of neurospheres and brain organoids in ZKV-infected fetal brains in cases of mother-to-fetus transmission of the infection12,13. ZKV has two significant lineages – African and Asian. Their role in pathogenicity and epidemiology is poorly understood; however, a correlation between microcephaly with the Asian lineage and fetal loss with the African lineage was seen. Although ZKV infection is not fatal, deaths are reported in pregnant females and immunocompromised patients. As an arboviral infection, ZKV infection has many overlapping signs and symptoms of its contemporary viruses like dengue, chikungunya, yellow fever, etc. Therefore, the WHO recommends molecular methods to detect viral RNA and serological tests for the early diagnosis of the infection and to rule out any dilemma. Blood (serum) is the sample of choice for the diagnosis of ZKV infection by both molecular and serological methods. However, urine, saliva, cerebrospinal fluid, placental tissue, semen, and amniotic fluid also can be used. Reverse transcriptase-PCR can do detection of viral RNA if the sample is collected within 10 days of infection, as low viral loads are detected after that duration. Serological tests are based on detecting serum immunoglobulin M by immunoglobulin M capture enzyme-linked immunosorbent assay and other platforms. However, there are chances of cross-reaction of serological tests with other Flavivirus infections; therefore, plaque reduction and neutralization assay can be used for confirmation. Multiplex methods like PCR to detect ZKV, dengue, and chikungunya is also available, along with reverse transcription loop–mediated isothermal amplification for dengue, influenza, and ZKV. Currently, there is no available treatment or vaccination for ZKV infection. Only symptomatic management with adequate rest, hydration, antipyretics, and analgesics other than NSAIDs (until dengue is ruled out), is recommended. In the current critical context of the ongoing COVID-19 pandemic, along with constant threats of multiple epidemics like monkeypox, measles, dengue, and chikungunya, we are not ready to tackle another onslaught of viral infection with grave consequences. The cases of two primary arboviral infections in India – dengue and chikungunya – have been rising for the past two consecutive years (2021 and 2022). Besides arboviral diseases, India tops the leaderboard for the highest measles cases in 2022. In a recently conducted retrospective study including serum samples of patients with febrile illness and negative for dengue and chikungunya, 64 samples were found to be positive for ZKV immunoglobulin M. Few positive samples were from patients of states and union territories not known to have ZKV cases ever before14. Moreover, in the constant threat of any time surge in COVID-19 cases due to its rapid mutation-prone nature, we must be prepared and constantly vigilant against emerging epidemic situations of potential culprits. The recent spike in COVID-19 cases in countries like China, Japan, Korea, Brazil, and the USA has added to such possibilities. ZKV has all the potential to create havoc in a setup like India, where there is a high density of vector Aedes mosquitoes, spreading other arboviral infections. The actual number of ZKV cases getting missed, where there is a high proportion of asymptomatic patients, along with poor diagnostic setup, similar clinical features like other arboviral infections causing dilemma, etc. In this situation, strengthening the diagnostic infrastructure, robust implementation of vector control measures, and remaining vigilant about every possible outbreak of ZKV and any such problem are of significant importance. Ethical approval Not applicable. Sources of funding None. Authors' contribution R.S., A.M., D.P., and B.K.P. developed the original draft, reviewed and edited the manuscript. All authors read and approved the final manuscript. Conflicts of interest disclosure The authors declare that they have no financial conflict of interest with regard to the content of this report. Research registration unique identifying number (UIN) Not applicable. Guarantor Ranjit Sah.